Permeability Alteration of Sarcolemmal Membrane in Catecholamine-induced Cardiac Muscle Cell Injury. In Vivo Studies with Fine Structural Diffusion Tracer Horse Radish Peroxidase

Cardiac muscle cell injury was produced in male Sprague-Dawley rats weighing 300 to 450 gm. with catecholamines, norepinephrine, and isoproterenol; sarcolemmal membrane alteration was tested in vivo using the extracellular macromolecular tracer, horseradish peroxidase. Norepinephrine was administered in continuous intravenous infusion in a dose of 4 to 6 mug. per 100 gm. of body weight per minute, whereas isoproterenol was given as a single subcutaneous injection in a dose of 8.5 mg. per 100 gm. of body weight. Horseradish peroxidase was injected intravenously and localized in the right ventricular myocardium following 6 and 30 minutes of circulation time by light and electron microscopy. As early as 10 minutes after norepinephrine infusion, horseradish peroxidase appeared within cardiac muscle cells possessing normal fine structure. Selective deposition of the tracer on normal and altered myofilaments was noted. Similar observations were made in the isoproterenol model at 60 to 90 minutes. The results indicate that sarcolemmal membrane permeability alteration is an early event in catecholamine-induced cardiac muscle injury. The possible functional significance of the findings is discussed.